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Ascorbic Acid Function and Metabolism

抗坏血酸的功能和代谢

基本信息

批准号：
7899389
负责人：
JAMES M. MAY
金额：
$ 10万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2010-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7899389
关键词：
Address Affect Animal Model Animals Antiatherogenic Antioxidants Apolipoprotein E Apoptosis Arterial Fatty Streak Ascorbic Acid Ascorbic Acid Deficiency Atherosclerosis Blood Vessels Cavia Cell Culture Techniques Cell Proliferation Cell Transplants Cell model Cell physiology Cells Collagen Collagen Type I Collagen Type IV Cultured Cells Diabetes Mellitus Diet Disease Endothelial Cells Fetal Liver Fibroblasts Foam Cells Functional disorder Generations Goals Hepatocyte Human Hypertension Kidney Diseases Lesion Lipopolysaccharides Low-Density Lipoproteins Mediator of activation protein Metabolism Modeling Modification Mus Myosin Heavy Chains Nature Nitric Oxide Peritoneal Macrophages Persons Principal Investigator Process Property Recycling Role Severities Smooth Muscle Myocytes Smooth Muscle Myosins Sodium Staging Testing Tocopherols United States Vascular Endothelial Cell Vitamin E Vitamins ascorbate atherogenesis cell dedifferentiation cell type improved macrophage men monocyte mouse model novel oxidant stress oxidized low density lipoprotein precursor cell prevent programs response vascular smooth muscle cell proliferation

项目摘要

Atherosclerotic cardiovascular disease remains the leading killer of men and wormen in the United States, especially in persons with diabetes, hypertension, and renal disease. Since treating humans in the late stages of atherosclerosis with vitamins C and E shows little benefit, this project targets the role of these antioxidant vitamins in the early stages of the process in cells and in mice prone to atherosclerosis. The rationale for this approach is the demonstration almost 50 years ago that moderate vitamin C deficiency in guinea pigs causes lesions indistinguishable from those of early human atherosclerosis. The first aim will evaluate vitamin C function in cell culture models of the three main cells involved in the atherosclerotic process: endothelial cells, vascular smooth muscle cells, and macrophages. Although antioxidant functions of vitamin C and interactions with vitamin E will be addressed, emphasis will be placed on how stimulation of collagen synthesis by vitamin C affects endothelial and smooth muscle cell proliferation and differentiation, and on how the vitamin can modify key macrophage functions as these relate to atherosclerosis. The second aim will utilize the ApoE-deficient mouse model of atherosclerosisto assess whether varying amounts intracellular vitamin C affect the progression, severity, and nature of the atherosclerotic lesions. Key to this aim is the use of mice that lack the ability to synthesize vitamin C in concert with mice that lack cellular transport of the vitamin. For example, using fetal liver cell transplants in lethally irradiated mice, it will be possible to test whether selective deficiency of vitamin C in macrophages lacking vitamin C transport worsens the atherosclerotic process. In the third aim, macrophages prepared from these animals will be cultured and used to define the role of differing intracellular vitamin C concentrations on macrophage function, and on antioxidant interactions with vitamin E. By focusing on mechanisms in cell models and on early disease in animal models, this project will show whether and how vitamin C prevents atherosclerosis.

动脉粥样硬化性心血管疾病仍然是美国男性和女性的头号杀手，